Recently, the number of patients with Alzheimer type dementia and cerebrovascular dementia is increasing at a remarkable rate in those countries with a rapidly aging population and this has become a serious social problem. Among these dementias, Alzheimer type dementia occurs due to neurodegeneration. It is symptom-free in its early development period. Once a patient is diagnosed with advanced stages the symptoms are irreversible and incurable with current medical technology. Therefore, a need exists for a bioactive substance that helps to reduce the risk of neurodegeneration and/or to delay the resultant symptoms.
Research is focusing on the clarification of the mechanism under which Alzheimer type dementia progresses and the development of new drugs to treat the condition. There have been a number of reports published. It has been found that patients with Alzheimer type dementia have similar brain abnormalities as those patients with basal forebrain cholinergic neuron syndrome (BFCN) which is also associated with loss of memory and learning capabilities due to neurodegeneration, neuronal atrophy, and neuronal loss. Because nerve growth factor (NGF) exerts a trophic action on BFCN, lack of NGF is considered to be one of the causes of these dementias. However, NGF is a protein, and may be degraded in the body and/or cannot pass through the blood-brain barrier when administrated orally. Therefore, it has become an objective of medical and pharmaceutical researchers in this area to discover or develop substances with low molecular weight which can pass through blood-brain barrier and induce the synthesis of NGF in the brain.
In addition, it has been reported that amyloid beta-peptide (Aβ) is one of the inducers of Alzheimer type dementia since it causes the inflammation and neurodegradation inside the neuron associated with Alzheimer's and leads to death as it accumulates in the brain. Therefore, the inhibition of the toxicities of amyloid beta-peptide is considered to be one of desired ways to prevent and treat the Alzheimer type dementia.
Some investigators have studied the inductive effects of NGF synthesis of H. erinaceum extracts. (See, for example, Kawagishi, et al. Tetrahedron Letters, 32 (35):4561-4564 (1991); Kawagishi, et al., Phytochemistry, 32(1):175-178 (1993); Japanese Patents Nos. 04-266848 and 04-275285.) Other investigators have reported the inhibitory effects of Aβ toxicity of different H. erinaceum extracts (See, Nagai, et al. J. Nutritional Chemistry, 17:525-530 (2006); Japanese Patent No. 3943399). The cited references all disclose extraction methods that utilize toxic organic solvents in the extraction procedures rendering them problematic for use in industrial or large scale extraction procedures designed to produce compounds for clinical use. In addition, the results disclosed in the references cited above are confined to in vitro experiments.
In this regard, because neurodegenerative diseases typically Alzheimer type dementia have a long incubation period prior to diagnosis, reducing the risk before the identification of visible symptoms of the disease is important. It would be advantageous to be able to reduce the risk of neurodegeneration by the consumption of food products if available and an important of option for target populations. Therefore, there is a need in the field for a method for extracting compounds from H. erinaceum using safe chemicals and shown to be effective in vivo.